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Open Access | Just Accepted

Effects of Different Proportions of n-3 and n-6 Polyunsaturated Fatty Acids on Cognitive Function in Mice

Lirong XuBeilei PangAiling TianMeifan PanZitong LiuKaixuan ChenXincen WangDuo Li( )

Institute of Nutrition and Health, Qingdao University, 266071, Qingdao, China

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Abstract

The n-3 and n-6 polyunsaturated fatty acids play an important role in nerve development and cognitive function. However, the effects of docosahexaenoic acid (DHA)/arachidonic acid (ARA) and linolenic acid (ALA)/linoleic acid (LOA) supplementation on cognitive function in mice have not been fully clarified. The purpose of this study is to explore the mechanism of different proportions of n-3 and n-6 fatty acids on cognitive function and hippocampus-related protein expression in mice, and to provide theoretical support for improving brain development and cognitive function in mice. After mice were given different proportions of ALA/LOA and DHA/ARA, the learning and memory abilities of mice were evaluated by Y-maze, open field and Morris water maze, and brain samples were collected to detect the morphology of hippocampal neurons and the expression of synaptic plasticity-related proteins. The results of Golgi Staining showed that the density of dendritic spines in ALA/LOA=1:1 and DHA/ARA=1:1 groups was significantly higher than that in the control group, which affected the synaptic structure of mouse neurons. DHA/ARA=1:4 and 1:1 groups up-regulated the expression of BDNF, TrkB, CREB and synaptic plasticity related proteins (PSD95, Syn, Snap) in hippocampus, increased the number of normal neurons in CA1 and CA3 areas of hippocampus, and significantly improved the cognition of mice. This study confirmed that DHA/ARA ratio of 1:4 and 1:1 can activate BDNF-TrkB-CREB signal axis, significantly enhance the learning ability of mice, and improve spatial memory (manifested by the increase of crossing times of Morris water maze platform) and working memory (manifested by the increase of the autonomous alternation rate of Y-maze), while the ratio of 4:1 will lead to metabolic disorder. It provides an important theoretical basis for optimizing the ratio of dietary fatty acids to promote cognitive function.

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Cite this article:
Xu L, Pang B, Tian A, et al. Effects of Different Proportions of n-3 and n-6 Polyunsaturated Fatty Acids on Cognitive Function in Mice. Food Science and Human Wellness, 2026, https://doi.org/10.26599/FSHW.2026.9251198

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Received: 13 November 2025
Revised: 06 January 2026
Accepted: 26 March 2026
Available online: 15 July 2026

© 2026 Beijing Academy of Food Sciences. Publishing services by Tsinghua University Press.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).